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Open Access Study protocol

Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial

Michael Walsh1*, Peter A Merkel2, Chen Au Peh3, Wladimir Szpirt4, Loïc Guillevin5, Charles D Pusey6, Janak deZoysa7, Natalie Ives8, William F Clark9, Karen Quillen10, Jeffrey L Winters11, Keith Wheatley12, David Jayne13 and on behalf of the PEXIVAS Investigators

Author Affiliations

1 Departments of Medicine and Clinical Epidemiology & Biostatistics, Marian Wing, Division of Nephrology, McMaster University, St. Joseph's Hospital, 50 Charlton Ave East, Hamilton, ON L8S 4A6, Canada

2 Division of Rheumatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

3 Department of Renal Medicine, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia

4 Department of Nephrology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

5 Höpital Cochin, Assistance Publique, Hopitaux de Paris, Universite Paris Descartes, Paris, France

6 Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK

7 Department of Renal Medicine, North Shore Hospital, Waitemata District Health Board, Auckland, New Zealand

8 Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK

9 London Health Sciences Centre, Western University, London, ON, Canada

10 Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA

11 Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN, USA

12 Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Birmingham, UK

13 Lupus and Vasculitis Clinic, Addenbrooke's Hospital, Cambridge, UK

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Trials 2013, 14:73  doi:10.1186/1745-6215-14-73

Published: 14 March 2013

Abstract

Background

Granulomatosis with polyangiitis (GPA, Wegener’s) and microscopic polyangiitis (MPA) are small vessel vasculitides collectively referred to as anti-neutrophil cytoplasm antibody-associated vasculitis (AAV). AAV is associated with high rates of morbidity and mortality due to uncontrolled disease and treatment toxicity. Small randomized trials suggest adjunctive plasma exchange may improve disease control, while observational evidence suggests that current oral glucocorticoid doses are associated with severe infections in patients with AAV. A randomized study of both plasma exchange and glucocorticoids is required to evaluate plasma exchange and oral glucocorticoid dosing in patients with AAV.

Methods/design

PEXIVAS is a two-by-two factorial randomized trial evaluating adjunctive plasma exchange and two oral glucocorticoid regimens in severe AAV. Five hundred patients are being randomized at centers across Europe, North America, Asia, and Australasia to receive plasma exchange or no plasma exchange, and to receive standard or reduced oral glucocorticoid dosing. All patients receive immunosuppression with either cyclophosphamide or rituximab. The primary outcome is the time to the composite of all-cause mortality and end-stage renal disease.

PEXIVAS is funded by the National Institute of Health Research (UK), the Food and Drug Administration (USA), the National Institutes of Health (USA), the Canadian Institute of Health Research (Canada), the National Health and Medical Research Council (Australia), and Assistance Publique (France). Additional in-kind supplies for plasma exchange are provided by industry partners (TerumoBCT, Gambro Australia, and Fresenius Australia).

Discussion

This is the largest trial in AAV undertaken to date. PEXIVAS will inform the future standard of care for patients with severe AAV. The cooperation between investigators, funding agencies, and industry provides a model for conducting studies in rare diseases.

Trial registration

Current Controlled Trials: (ISRCTN07757494) and clinicaltrials.gov: (NCT00987389)

Keywords:
Factorial trial; Randomized controlled trial; Protocol; Vasculitis; Granulomatosis with polyangiitis; Microscopic polyangiitis; ANCA